The studies in this proposal will use in vivo whole cell recordings to determine the various circuits that form EI cells in the inferior colliculus (IC), an the functional impacts of those circuits. We showed in previous extracellular studies that EI cells comprise a diverse group due to the various circuits that generate the same EI property among the IC population [4,10-12,18]. We recently used whole cell recordings to confirm that the various monaural and binaural inputs proposed in our previous extracellular studies could be observed in the sound evoked post-synaptic potentials (PSPs) [25]. In most EI cells, the patterns of sound evoked PSPs showed projections that were unexpected, since extracellular recordings gave no hint of their presence. In a pilot study we also evaluated the circuitry in a new way, by computing the excitatory and inhibitory conductances that underlie monaural and binaural responses. That circuitry was even more surprising since additional inputs were revealed that were not apparent even from the sound evoked PSPs. One of the unexpected inputs is from the dorsal nucleus of the lateral lemniscus (DNLL). The DNLL is special because its cells express a unique pattern of ipsilateral evoked inhibition and it provides a strong inhibitory innervation to the IC, which can have profound influences on IC responses to dynamic IIDs [12, 25]. The circuitry revealed by both PSPs and conductances suggests that most EI cells should respond selectively to dynamic binaural signals with IIDs that change over time. It was these surprising results, especially the unexpected circuitry revealed by conductances and the exciting response features they suggest, that prompt the studies in this proposal. The studies will identify the inputs that evoke both monaural and binaural responses in each type of EI cell by recording spikes, postsynaptic potentials (PSPs) and by computing the excitatory and inhibitory conductances that generate each response. The circuits derived from the conductances show how and why each EI type responds to both IIDs presented one at a time (static IIDs) and suggest how each EI type should respond to dynamic IIDs that change over time, such as moving sound sources or multiple sounds that emanate from different regions of space. The cells will then be tested with those dynamic binaural stimuli and the responses will be compared to the responses predicted from the circuitry derived from conductances. In addition, simple tests will be administered that provide insights into whether or not each cell receives inputs from one or both DNLLs. This information will provide insights into how the auditory system handles binaural information in complex acoustic environments, including how it deals with multiple sound sources in space. Such information could be translated into algorithms that might prove useful in robotics and/or in the construction of hearing aids for the hearing impaired. PUBLIC HEALTH RELEVANCE: The proposed studies focus on how the auditory system handles binaural information in complex acoustic environments, including how it deals with multiple sound sources in space. Such information could be translated into algorithms that might prove useful in robotics and/or in the construction of hearing aids for the hearing impaired.